We are currently enhancing the computational efficiency of our flexible ligand docking program DIVALI There are two parallel tracks that are being adopted: (1) increasing the computational efficiency of the genetic algorithm in sampling space and (2) docking using alternative functional forms, namely surface based descriptors and empirical binding free energy descriptors. The algorithmic changes include the adoption of ideas from "interval arithmetic" and its incorporation within the evolutionary algorithm that forms the basis of DIVALI. Preliminary results on complicated functions in high dimensions are extremely promising. We are currently evaluating different empirical free energy methods for flexible ligand docking and comparing them with the original AMBER-based descriptors in DIVALI.